Environmental stress is recognized as a major cause of infertility in men and women. However, it is not clear how stressful stimuli interrupt normal reproductive processes. The recent isolation and purification of corticotropin-releasing hormone (CRH) has provided a valuable new tool for investigating the relationship between stress and infertility. CRH is a peptide synthesized in the brain and released into the hypophyseal portal system where it regulates activation of the adrenal cortex by the pituitary. Several recent studies have provided evidence supporting the hypothesis that, in addition to the other suppressive effects of stress on reproductive processes, CRH may directly inhibit the release of gonadotropin- releasing hormone (GnRH), a peptide required for pituitary activation of the gonads. The long-term goal of this investigation is to define the physiological and environmental control of reproductive processes in non-human primate species that demonstrate reproductive patterns similar to those found in humans. This proposal describes experiments that will provide insight into the physiological mechanisms through which stress affects fertility in male and female macaques. The body responds to an environmental stimulus with the release of a variety of chemical signal; the goal of this line of research is to isolate the effects of CRH on gonadotropin secretion. The first aim is to analyze and compare the effects of a specific stressful situation (i.e., short-term chair restraint) on male and female ,acacias on different reproductive states. All of the animals used in these studies will have indwelling catheters which will allow blood sampling and delivery of test substances from a remote site. The second aim of this study is to determine if CRH can inhibit the secretion of pituitary gonadotropins when injected into an unstressed animal. Thirdly, an antagonist to CRH will be administered immediately before exposing an animal to a stressful stimulus to determine if blocking the inhibitory effects of endogenous CRH on gonadotropin secretion will elucidate the physiologic role that CRH has in controlling fertility. The fourth aim is to test whether neuroleptic drugs that are known to block the release of gonadotropins from the pituitary do so indirectly by stimulating the release of CRH which then blocks GnRH release. Several neuroleptic drugs are thought to act by inhibiting the action of neurotransmitters on GnRH neurons. Environmental stress is a contributing factor in many human diseases. The final aim, once the specific agent that inhibits gonadotropin release during stress has been identified, is to determine if chronic administration of this agent will result in infertility. A better understanding of the mechanisms which activate the hypothalamic-pituitary-adrenal axis in response to stress will also clarify the effects of stress on other physiological systems and will allow the development of more effective strategies to cope with everyday stress.